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Low-concentration HCP1 inhibits apoptosis in vascular endothelial cells

Author:
Wei, Qun, Zhang, Jun, Su, Le, Zhao, Xuan, Zhao, BaoXiang, Miao, JunYing, Lin, ZhaoMin
Source:
Biochemical and biophysical research communications 2019 v.511 no.1 pp. 92-98
ISSN:
0006-291X
Subject:
apoptosis, blood serum, endoplasmic reticulum, fibroblast growth factor 2, heat-shock protein 90, human umbilical vein endothelial cells, humans, lung neoplasms, neoplasm cells, vascular diseases
Abstract:
Vascular endothelial cell (VEC) apoptosis takes part in the development of various cardiovascular diseases. Heat shock protein 90 (HSP90) regulates apoptosis through various apoptosis associated client proteins. In previous study, we identified a novel HSP90 inhibitor HCP1 induced apoptosis in A549 human lung cancer cells. Here, we found that low-concentration HCP1 (1 μM, 2 μM) suppressed VEC apoptosis caused by serum and fibroblast growth factor 2 (FGF-2) deprivation. HCP1 directly bound to glucose-regulated protein 94 (Grp94), an isoform of HSP90 located in endoplasmic reticulum, and HCP1 selectively inhibited Grp94 activity via binding to site 3. Overexpression of Grp94 inhibited the anti-apoptotic effect of HCP1 in human umbilical vein endothelial cells. Therefore, we provided HCP1 as a new VEC apoptosis inhibitor which might be a potential compound in the treatment of VEC apoptosis related vascular diseases. And we provided new pieces of evidence to understand the role of Grp94 in VEC apoptosis.
Agid:
6301097